ArticleProceedings of the National Academy of Sciences of the United States of America2017
Immunoreceptor tyrosine-based inhibitory motif-dependent functions of an MHC class I-specific NK cell receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Natural language processing of gene descriptions for overrepresentation analysis with GeneTEA.Genome biology · 2025Article
- Article
- Expression of a single inhibitory member of the Ly49 receptor family is sufficient to license NK cells for effector functions.bioRxiv : the preprint server for biology · 2024Article
- SingleCellGGM enables gene expression program identification from single-cell transcriptomes and facilitates universal cell label transfer.Cell reports methods · 2024Article
- Altered-Self MHC Class I Sensing via Functionally Disparate Paired NK Cell Receptors Counters Murine Cytomegalovirus gp34-Mediated Immune Evasion.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Dynamic variability in SHP-1 abundance determines natural killer cell responsiveness.Science signaling · 2021Article
- Licensing Natural Killers for Antiviral Immunity.Pathogens (Basel, Switzerland) · 2021Review
- Donor KIR3DL1/receptor HLA-Bw4-80I Combination Reduces Acute Leukemia Relapse after Umbilical Cord Blood Transplantation without in Vitro T-cell Depletion.Mediterranean journal of hematology and infectious diseases · 2021Article
- Immune checkpoint molecules in natural killer cells as potential targets for cancer immunotherapy.Signal transduction and targeted therapy · 2020Review
- Control of Viral Infection by Natural Killer Cell Inhibitory Receptors.Cell reports · 2020Article
- Inducible down-regulation of MHC class I results in natural killer cell tolerance.The Journal of experimental medicine · 2019Article
- CD8Frontiers in immunology · 2019Article
- Natural killer cells might adapt their inhibitory receptors for memory.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Novel natural killer cell-mediated cancer immunotherapeutic activity of anisomycin against hepatocellular carcinoma cells.Scientific reports · 2018Article
- Natural Killer Cell Education and the Response to Infection and Cancer Therapy: Stay Tuned.Trends in immunology · 2018Review
- Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Natural killer (NK) cells express MHC class I (MHC-I)-specific receptors, such as Ly49A, that inhibit killing of cells expressing self-MHC-I. Self-MHC-I also "licenses" NK cells to become responsive to activating stimuli and regulates the surface level of NK-cell inhibitory receptors. However, the mechanisms of action resulting from these interactions of the Ly49s with their MHC-I ligands, particularly in vivo, have been controversial. Definitive studies could be derived from mice with targeted mutations in inhibitory Ly49s, but there are inherent challenges in specifically altering a single gene within a multigene family. Herein, we generated a knock-in mouse with a targeted mutation in the immunoreceptor tyrosine-based inhibitory motif (ITIM) of Ly49A that abolished the inhibitory function of Ly49A in cytotoxicity assays. This mutant Ly49A caused a licensing defect in NK cells, but the surface expression of Ly49A was unaltered. Moreover, NK cells that expressed this mutant Ly49A exhibited an altered inhibitory receptor repertoire. These results demonstrate that Ly49A ITIM signaling is critical for NK-cell effector inhibition, licensing, and receptor repertoire development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.